Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Compounds and methods useful for treating or preventing hematological cancers

Active Publication Date: 2018-09-20
BAYER PHARMA AG +3
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text is about a mixture of a compound with a carrier that helps to administer the compound to a person. The carrier is safe and will not harm the patient in any way. The text also explains the term "treat," which means reducing symptoms of a disease or condition by giving an agent or compound to the person.

Problems solved by technology

These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection.
As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.
One approach for a 10% subset of patients diagnosed with acute promyelocytic leukemia (APL) has achieved limited success in AML comprising treating the subject with small molecules, such as all-trans retinoic acid (ATRA) and arsenic trioxide, that trigger the differentiation of the leukemic AML cells.
Unfortunately, differentiation therapy does not exist for the much larger fraction of non-APL acute myeloid leukemias, where the standard of care results in an overall survival rate of only 25%.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compounds and methods useful for treating or preventing hematological cancers
  • Compounds and methods useful for treating or preventing hematological cancers
  • Compounds and methods useful for treating or preventing hematological cancers

Examples

Experimental program
Comparison scheme
Effect test

example 1

A9 Fusion Establishes a Model of Conditional Myeloid Differentiation Arrest

[0212]High-throughput myeloid differentiation assays are challenging, as specific measures of myeloid differentiation are cumbersome and have historically relied on morphologic or enzymatic assays or more recently on changes in gene expression. Furthermore, myeloid differentiation has typically been assessed in AML cell lines where the mechanism of differentiation arrest is not defined.

[0213]An estrogen receptor-HoxA9 (ER-HoxA9) fusion protein was used to immortalize cultures of primary murine bone marrow conditionally. The persistent expression of the wild-type HoxA9 protein is sufficient to enforce myeloid differentiation arrest in cultures of murine bone marrow, and injection of these cells into recipient mice leads to acute myeloid leukemia (AML), albeit with a long latency (Kroon et al., The EMBO Journal 17, 3714-3725, 1998). Fusion of the hormone-binding domain of the human estrogen receptor (ER) to the...

example 2

GFP-ER-HoxA9 Cells Establish a Model for a Phenotypic Screen of AML Differentiation

[0215]In order to facilitate a small-molecule differentiation screen, an ER-HoxA9 GMP cell line was derived from the bone marrow of the lysozyme-GFP (green fluorescent protein) knock-in mouse, in which the expression of GFP is limited to mature myeloid cells. Time-course gene-expression analysis by RNA-sequencing (RNA-Seq) was performed on undifferentiated cells cultured in beta-estradiol as well as at 9 time points following the removal of beta-estradiol, up to 120 hours. The pattern of expression of key neutrophil genes (Elane, Mpo) as well as HoxA9 target genes (Cd34, Flt3) demonstrates the expected stepwise pattern of transcription factors, primary granule proteins, and secondary granule proteins (FIG. 1E). Gene expression was compared to that of unmanipulated cultures of primary murine myeloblasts allowed to differentiate in vitro over 7 days (FIGS. 1F, 1K, 1L, as well as to freshly sorted subset...

example 3

roughput Screen Identifies 12 Small Molecules as Mediators of Myeloid Differentiation

[0218]Using the Lys-GFP-ER-HoxA9 GMPs, a high-throughput small-molecule phenotypic screen was performed to identify compounds that could trigger myeloid differentiation in the presence of active HoxA9. (See Example 20 for assay details.) After four days of compound treatment, cells were assessed by high-throughput flow cytometry for viability based on forward and side-scatter properties, and for differentiation as determined by the endogenous expression of GFP and cell-surface expression of CD11b (APC fluorescence, FIG. 2C). The assay achieved a Z-factor of 0.9, indicating an excellent signal-to-noise ratio. The differentiation potential of more than 330,000 small molecules within the NIH Molecular Library Program's Molecular Library Small-Molecule Repository (MLSMR) library was assessed over approximately 25 screening days.

[0219]Active compounds were re-screened by flow cytometry in concentration-r...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Timeaaaaaaaaaa
Timeaaaaaaaaaa
Timeaaaaaaaaaa
Login to View More

Abstract

The present invention includes methods of treating patients with acute myeloid leukemia across a range of genetic subtypes with DHODH inhibitors, such as 6-fluoro-2-(2′-fluoro-[1,1′-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid).

Description

BACKGROUND OF THE INVENTION[0001]Acute myeloid leukemia (AML), also known as acute myelogenous leukemia or acute non-lymphocytic leukemia (ANLL), is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease (accounting for approximately 1.2% of cancer deaths in the U.S.) its incidence is expected to increase as the population ages.[0002]The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Several risk factors and chromosomal abnormalities have been identified, but the specific cause ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/47A61P35/02A61K33/36A61K31/42A61K31/277
CPCA61K31/47A61P35/02A61K33/36A61K31/42A61K31/277A61K31/27A61K31/505
Inventor SYKES, DAVID B.SCADDEN, DAVIDLEWIS, TIMOTHY A.JANZER, ANDREASMEYER, HANNASTÖCKIGT, DETLEF
Owner BAYER PHARMA AG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com